Prevention investigators in our Center and elsewhere have demonstrated that drug abuse prevention efficacy can be significantly enhanced by targeting individuals who are most vulnerable to developing problems and tailoring message content and format based on the characteristics of these individuals. Our previous work focused on drug use initiation and identified behavioral mechanisms (neurobehavioral response to reinforcing, novel and emotional stimuli) whereby the sensation seeking dimension of impulsivity is associated with vulnerability to drug use initiation and high sensation-value contexts enhance the efficacy of prevention interventions designed to reduce drug use initiation. Further development of laboratory models to identify individuals who are vulnerable to drug use escalation and development of associated problems and identifying the characteristics of these individuals that predispose them to vulnerability and/or influence the efficacy of targeted intervention materials is of critical importance for informing and advancing the field of drug abuse prevention. This application proposes five years of research to continue laboratory investigations of individual differences associated with drug use escalation and associated exposure to heavy drug use. Growing evidence suggests that vulnerability to drug-use escalation is associated with self-control mechanisms. A multidisciplimary approach combining personality measurement with laboratory abuse liability assessment, behavioral inhibition task performance and brain imaging methodologies will be used to examine impulsivity among matched groups of tobacco and marijuana users who have either maintained stable patterns of intermittent/light use (escalation resistant) or who have escalated to heavy use with and without extended histories of heavy use (escalation; escalation + extended drug exposure) to test the hypothesis that drug use escalation is associated with inhibitory neurobehavioral dimensions of impulsivity. Knowledge of the association between component dimensions of impulsivity and drug-use escalation will enhance understanding of vulnerability to and consequences of drug use escalation and thus our ability to design more efficacious tailored and targeted drug abuse prevention interventions. RELEVANCE (See instructions): Drug abuse prevention efficacy is improved by targeting at-risk individuals and tailoring interventions based on the characteristics of those individuals. Impulsivity is closely linked with drug abuse vulnerability. This project will support prevention science by identifying the neurobehavioral dimensions of impulsivity that are associated with vulnerability to and adverse consequences of tobacco and marijuana use escalation.